title: In situ evaluation of kinetic resolution catalysts for nitroaldol by rationally designed fluorescence probe.
abstract: Development of effective chemical catalysts is a key concern in organic chemistry. Therefore, convenient screening systems for chemical catalysts are required, and although some fluorescence-based HTS systems have been developed, little attempt has been made to apply them to asymmetric catalysts. Therefore, we tried to develop a chiral fluorescence probe which can evaluate the reactivity and enantioselectivity of asymmetric catalysts. We focused on kinetic resolution catalysts as a target of our novel fluorescence probe, employing β-elimination following acylation of nitroaldol. Once the hydroxyl group of nitroaldol is acylated, β-elimination occurs immediately, affording nitro olefin. Therefore, we designed and synthesized a fluorescence probe with an asymmetric nitroaldol moiety. Its fluorescence intensity decreases dramatically upon β-elimination, so the fluorescence decrease is an indicator of the reaction yield. Thus, the enantioselectivity of kinetic resolution catalysts can be assessed simply by measuring the fluorescence intensities of the reaction mixtures of the two enantiomers; it is not necessary to purify the product. This fluorescence probe revealed that benzotetramisole is a superior catalyst for kinetic resolution of nitroaldol. Furthermore, we established an HTS system for asymmetric catalysts, using a fluorescence probe and benzotetramisole. To our knowledge, this is the first fluorescence-based HTS system for asymmetric catalysts.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mori
authors.forename: Takuya
authors.initials: T
authors.lastname: Terai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
mesh_terms: D001896:Boron Compounds / Q000737:chemistry; D002384:Catalysis; D015195:Drug Design; D005456:Fluorescent Dyes / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry*; D007700:Kinetics; D009574:Nitro Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D009574:Nitro Compounds; C560828:nitroaldol